The present invention is directed to the use of colloidal-size particles to realize microfluidic and photonic devices.
The xe2x80x9clab-on-a-chipxe2x80x9d concept, in which three-dimensional microfabrication techniques borrowed from the integrated circuit industry are employed to create electrical circuits that interface with chemical or biological systems upon micropatterned substrates, has gained significant research interest in recent years, and has been heralded as the next silicon revolution. The drastic reduction in length scales from conventional techniques to microelectrical-mechanical systems (MEMS) will allow tasks to be performed more rapidly, efficiently, and on smaller sample volumes than ever before. Functional systems fabricated to exploit this microscale fluid motility possess great promise to significantly streamline processes for fundamental research and medical applications in areas such as bioanalysis, medical diagnostics and therapeutics. Such developments will enable a large-scale shift from centralized laboratories to remote point-of-care and benchtop diagnostic facilities.
Initially, single devices such as pumps, valves, mixers, filters, and sensors have been developed to perform individual tasks on microfluidic samples. Seamlessly integrating individual devices capable of single operations will finally bring to fruition the promise of micro total analysis systems (xcexcTAS) as portable laboratories, chemical production facilities, remediation units, health monitors and countless other applications which would benefit from miniaturization. In order to construct such devices, however, a common platform must be developed which allows for complete control of heterogeneous or complex fluids as well as specifically targeted sensing and feedback actuation.
Generally, the utility, speed and performance of microfluidic chips increases as the overall device size decreases, particularly for devices that are ultimately designed for human implantation. The need to mix, administer and separate fluids at these length scales has long been a limiting factor in such devices. Specifically, the ultimate size of microfluidic devices has been restricted by the size of the actuator, which can be classified as either those micromachined specifically for microfluidic application or conventional actuators that have been miniaturized for integration with microfluidic devices. Examples of the latter include electromagnetic plungers connected to pneumatic systems, miniature piezoelectrics and memory alloys. Such actuators function well, but must be affixed to the microfluidic chip as additional hardware with epoxy resin. Actuators that may be micromachined, such as electrostatic, thermopneumatic, electromagnetic and bimetallic actuators consume significantly less space than conventional actuators but often require difficult etching procedures.
Microfluidic flow controllers, such as chip-top valves and pumps, have also historically been plagued by size limitations imposed by actuators. The first microvalve consisted of a silicon seat with a nickel diaphragm actuated by a solenoid plunger and measured approximately 3 mm. Subsequently, as piezoelectric stacks, electromagnetic alloys and thermopneumatics became fashionable, microvalves and reciprocating micropumps became smaller, but continue to dwarf the scale of microchannels and other chip-top features. More recently, electroosmosis, which requires no moving parts and overcomes some of these limitations, has experienced success as a viable means of microfluidic flow generation and control. This technique is quite efficient at transporting and separating ionic liquids and relies upon the principle of electrophoresis, the migration of ions in an electric field, and the resulting osmotic pressure gradient to induce the flow of bulk fluids.
While some current microfluid handling devices and techniques enable functional devices at microscales, they may also impose significant constraints upon potential device capability, flexibility and performance. For instance, electroosmotically driven flow requires complex circuitry, a high-voltage power supply and is dependent upon the ionic properties of the solution and has the potential to separate components of the solution from the bulk. While molecular separation by electrophoresis has been exploited for particular applications such as nucleic acid sequencing and the development of protein targeted chemotherapy, the complications discussed here are generally considered obstacles to xcexcTAS intended for applications with heterogeneous fluids such as blood or urine. Additionally, the scale of flow controllers, such as pumps and valves, has not kept pace with the miniaturization of flow channels themselves, thus limiting the ultimate size at which practical devices may be created. Recent efforts have made strides to overcome the limitations of traditional materials and techniques; for example, a first-generation pumping and valving system fabricated completely from elastomeric materials allows for in situ fluids control on length scales below 100 xcexcm. While functionally simple and conceptually elegant, the pneumatic actuation scheme still hinders the ultimate utility of these devices through the need for interfacing to external equipment. To completely integrate fluidic processes upon a single chip, the current paradigms of microfluids handling must be abandoned in favor of units that are of equivalent size to the process into which they are being imbedded. An attempt to achieve these ends has been made using xe2x80x9csmartxe2x80x9d hydrogel structures fabricated directly within microfluidic networks (xcexcFNs). These structures, while only tens of microns in size and very efficient at measuring and responding to specific environmental conditions, such as pH and temperature, are quite limited in their sensing capabilities and ability to produce a broad range of feedback options. Additionally, these structures have demonstrated only the ability to regulate flow, not initiate it. Integrating simultaneous microscale fluid pumping and valving completely on the microscale is a key component to the development of xcexcTAS.
Microscale devices designed to accomplish specific tasks have repeatedly demonstrated superiority over their macroscale analogues and in many cases have proven capable of performing functions not possible on the macroscale. The advantages of such devices are due largely to unique transport properties resulting from low Reynolds number flows (Re less than 1) and vastly increased surface to volume ratios. Additionally, microfluidic processes may be easily parallelized for high throughput and require vastly smaller sample volumes; a significant benefit for applications in which reagents or analytes are either hazardous or at a premium. In general, the utility, speed and performance of Microsystems increase as the overall device size decreases. The need to mix, pump, and direct fluids at very small length scales, however, has long been the limiting factor in the development of microscale systems, thus generating a tremendous amount of interest in the burgeoning field of microfluidics. As improved actuation techniques have become available, conventional valving and pumping schemes have been miniaturized yet continue to dwarf microchannels and other chip-top features. Recently, several approaches conceived explicitly for the microscale have been developed including platforms based upon electrohydrodynamics, electroosmosis, interfacial phenomena, conjugated materials, magnetic materials and multilayer soft lithography. While these microfluid handling techniques enable functional devices on microscopic length scales, they also impose unique constraints upon potential device capability, flexibility and performance. To fully integrate multiple fluidic processes within a single microsystem, methods for microfluid handling must be developed which are accommodating to fluids of complex and dynamic composition and are of comparable size to the processes into which they are being imbedded. By reducing the size of these physical units, large device arrays can be fabricated on the same xe2x80x9cchip topxe2x80x9d and will be capable of accomplishing chemical and biochemical tasks and analyses of vastly increased complexity on samples of microscopic quantity.
Development of devices that can function at these length scales has centered around complex fabrication schemes for intricate components such as gears, cantilevers and other microscale objects. The fabrication and actuation of these devices, however, has been limited to bulk environments external to microfluidic geometries. Because no practical implementation scheme has been developed for their incorporation into functioning microfluidic systems, they have not realized their suggested potential as microfluidic pumps and valves.
Colloidal Photonics
The controlled assembly of colloidal particles has received significant attention in recent years because of the potential application of nano- and micro-structured materials in many fields. Ordered colloidal systems have lattice spacings ranging from nanometers to microns and therefore can diffract ultraviolet, visible, and near-infrared light. One can take advantage of this property for a variety of applications, including sensors, narrow-band optical filters, optical switches, photonic band gap materials, waveguides, and other types of optical and electrooptical devices. Photonic crystals, spatially periodic arrays in a medium of different dielectric constant, are of particular interest and are designed to affect the propagation of electromagnetic waves in much the same way that semiconductors influence the movement of electrons. First proposed in 1987, they could lead to the miniaturization and high-speed performance of integrated circuits and have profound applications for telecommunications, lasers, fiber optics, data processing and display technologies, as discussed in the Basic Energy Sciences report xe2x80x9cNanoscale Science Engineering and Technology Research Directionsxe2x80x9d xe2x80x9c . . . photonic-crystal structures have immense potential for a large variety of optoelectronics devices.xe2x80x9d In addition, this report points out the length scales required for manipulation of visible light: xe2x80x9cTo create photonic crystals operating at optical wavelengths the smallest feature sizes must be of the order of 100 nm, clearly in the realm of nanotechnology.xe2x80x9d
To date, the primary difficulty in the use of colloidal systems for such applications has been the fabrication of large arrays of colloidal particles into specific lattices with specific defect structures and tailored optical properties. Ordering in these systems is thermodynamically driven by colloidal interactions that may be predominantly attractive or repulsive, interactions that can often be readily tuned. For example, in a colloidal dispersion, repulsions can be modified by changing solution ionic strength and attractions can be influenced by solvent index matching or by varying salt concentration. However, development of technologically relevant colloidal crystals is hindered by the difficulty in uncoupling the variation of colloid-colloid interactions from the lattice structures that do form. Often for a specific application one wishes to manipulate colloidal surface chemistry, intervening fluid, or the specific colloidal material, all of which influence the nature of the crystallization process and may inhibit the formation of a particular lattice structure. A means of ordering colloidal particles that does not rely upon surface or particle chemistry will greatly aid the use of colloidal crystallization for technological applications. For this reason, the approach has been to aid and control the ordering of colloidal systems using applied external fields.
The present invention provides a device in which colloidal-size particles are utilized in a structure that is used to manipulate microfluidic streams or flows, including streams or flows in which particles are dispersed. Generally, a microfluidic device that utilizes colloidal-size particles comprises an input structure for receiving a microfluidic flow or stream, an output structure for transmitting a microfluidic stream, a space between the input and output structures, a colloidal structure located in the space, and a device for applying a field to the colloidal structure that causes the colloidal structure to move and thereby manipulate a microfluidic flow between the input and output structures. Among the possible fields that can be applied is an electrical field that has a component that is parallel to the direction in which an electrically charged colloidal structure is to move. Movement of the colloidal structure in this case is accomplished by electrophoresis. Another possible field is an electrical field that has a component that is normal to a plane in which two or more colloidal particles are substantially confined to two-dimensional movement. The electric field induces a dipole-dipole repulsive force between the colloidal particles. A further possible field is a magnetic field that has a component that is parallel to the direction in which a colloidal particle with a magnetic dipole is to move. Yet another possible field is an electromagnetic field. One technique for applying an electromagnetic field to a colloidal structure is known as an optical trap because light is used to hold a colloidal particle at a desired location or move a colloidal particle to a desired location. Among the optical trap techniques are optical xe2x80x9ctweezersxe2x80x9d and the scanning laser optical trap (SLOT) technique.
In one embodiment, a microfluidic two-way valve is provided in which the flow of a microfluidic stream between an inlet port and an outlet port is controlled by moving a colloidal particle between a position that blocks the flow and a position that permits the flow to occur. In one embodiment, two other colloidal particles that are fixed in place and an electrode structure for producing an electrical field with a normal component are utilized to move the colloidal particle to the desired position using dipole-dipole repulsion. In other embodiments, electrophoresis, magnetic fields and optical trapping are utilized to position a colloidal particle to control the flow between input and output ports. Valves having only one input port and multiple output ports, multiple input ports and a single output port, and multiple input and output ports are also feasible.
In another embodiment, a microfluidic pump is provided that is capable of pumping a microfluidic flow between the input and output structures. In one embodiment, a microfluidic peristalsis pump is provided that includes a closed loop that is disposed in the space between the input and output structures with a portion of the loop placed along a line between the inlet and outlet structures. The positions of a plurality of colloidal particles located in the closed loop is manipulated to achieve the pumping action. In one embodiment, one colloidal particle is moved from a point adjacent to the input structure to a point adjacent to the output structure along the noted portion of the loop to pump a portion of the microfluidic flow received at the input structure to the output structure. While this is occurring, two other colloidal particles are used to block any of the flow from entering the other portion of the closed loop. Once the first colloidal particle has completed the pump, the particles are rotated within the loop to pump the next portion of the microfluidic flow received at the input structure. Any of the various fields can be applied to position and move the colloidal particles. In another embodiment, a microfluidic peristalsis pump is provided in which colloidal particles are positioned in a string and the position of the colloidal particles in the string is manipulated over time so that the string goes through a sinusoidal type of motion that pumps a microfluidic flow. Another embodiment of a microfluidic pump that utilizes colloidal particles includes a rotating hub, an arm that extends from the hub, and a colloidal particle attached to the arm. Any of the noted fields are applied to move the arm and thereby achieve pumping action. In yet a further embodiment, two pairs of colloidal particles are manipulated to realize a two-lobe gear pump. More specifically, one pair of colloidal particles is rotated in a clockwise direction and the other pair of particles is rotated in a counter-clockwise direction to achieve the pumping action between the input and output structures.
The present invention further provides a photonic device that utilizes colloidal particles to manipulate light. Generally, the photonic device comprises a structure for strictly confining a plurality of colloidal particles to two dimensional movement. Typically, the structure is a pair of parallel plates and the colloidal particles are spherical. In such an embodiment, the plates are separated from one another by less than twice the diameter of the smallest diameter colloidal particle disposed between the plates, thereby substantially inhibiting the establishment of three-dimensional colloidal structures and substantially limiting movement of the colloidal particles to two-dimensional movement (i.e., strictly constrained movement). The photonic device further comprises a structure for applying an electric field that has a component that is normal to the plane in which the colloidal particles are confined. The application of such an electrical field to strictly constrained colloidal particles causes the colloidal particles to repel one another and thereby establish an order or crystalline structure among themselves. The photonic device further comprises a structure for directing light into the space occupied by the colloidal particles.
In one embodiment, a photonic waveguide is provided that allows light to be directed along a path through the colloidal particles. The photonic waveguide comprises the previously noted elements of a photonic device and a device for defining the path along which light is to propagate when the colloidal particles are in an ordered state. In one embodiment, a wall is established between the plates that prevents colloidal particles from being located in the space between the plates that is occupied by the wall. In another embodiment, the path is defined by an optical trap. The use of an optical trap allows the path along which light is to propagate to be changed over time. In another embodiment, a second electrical field that has a greater magnitude is used to define the path. Regardless of the structure used to establish the path, when no electrical field is being applied to the colloidal particles, the colloidal particles are in an unordered state that causes any light directed into the space occupied by the colloidal particles to be scattered. However, when an electrical field is applied to the colloidal particles, the colloidal particles enter an ordered state and light directed into the defined path propagates along the path.
In another embodiment, a photonic filter or switch is provided that utilizes the diffraction property of ordered colloidal particles. In one embodiment, the photonic filter or switch comprises the previously noted elements of a photonic device and a pair of polarizers that are crossed relative to one another, with one polarizer associated with each plate. When no electrical field is being applied to the colloidal particles, the unordered state of the colloidal particles prevents white light from passing through the crossed polarizers. However, when an electrical field is applied to the colloidal particles to place the particles in an ordered state, certain frequencies of white light are depolarized and capable of passing through both polarizers. By stacking such structures, different colors or changes in intensities are achieved. In another embodiment, the cross polarizers are eliminated. In this embodiment, when no electrical field is being applied to the colloidal particles, white light passes through both plates. However, when an electrical field is applied to the colloidal particles, white light directed to one of the plates is diffracted by the ordered colloidal particles such that an observers appropriately positioned relatively to the other plate will observe certain frequencies of white light, i.e., certain colors. This embodiment is also capable of being used to selectively reflect light.